These studies continue our work on the genetic sturcture of the major histocompatibility complex (MHC) of the rat and the effects of this structure on the immunological functions controlled by the complex. They utilize the resources of our colony of 22 inbred strains, 19 congenic lines, 3 natural recombinants, 2 laboratory-derived recombinants and over 300 different antisera. A recessive morphological marker, the m locus, linked to the MHC has been discovered, and it will be used in a three point cross to orient the Ag-B and MLR loci in the MHC. The question of two serologically defined loci in the MHC will be addressed in an outcross experiment employing two congenic lines. All of our congenic lines will be analyzed for recombinations within the MHC, and the two recombinants between Ag-B and immune responsiveness that have already been identified will be studied in detail to determine the basis for the loss of responsiveness. More basic information for studies on the genetic control of the immune response will be obtained by examining the response in representative strains to a selected group of synthetic polypeptide, protein and DNP-protein antigens. The polygenic control mechanism will be explored further by trying to separate its two major autosomal components into separate lines using rats with high responder haplotypes from F2 and backcross populations that have lost their ability to respond and by studying the genetic control of antigenic competition. The availability of several Y congenic lines on high and low responder backgrounds will allow us to investigate the potential role of Y-associated factors in the lower antibody responses of males. Our data on the segregation of responsiveness in various crosses will be used to develop a more sophisticated model of the genetic control mechanism using computer simulation techniques. Finally, we will collaborate in studies on kidney and heart transplantation, the response to parasitic and viral infections and the response to tumors and in providing reference testing of strains and reagents for our colleagues. The functional importance of such features of the MHC as the order and location of the genes and the degree of polymorphism of the individual loci must be established. The organization of the MHC in the rat is probably like that in man; hence, it will be a useful model for such studies relevant to man as organ transplantation or susceptibility to infection. (Text Abridged.)